1,2-Dichloroethane → (1-(4-fluorobenzyl)-1H-indol-2-yl)(4-(hydroxymethyl)piperidin-1-yl)methanone

HRID 83661Notes

Reaction equation

HRID 83661 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16](O)=[O:17])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH:44]1[CH2:49][CH2:48][CH:47]([CH2:50][OH:51])[CH2:46][CH2:45]1>CN(C=O)C>[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[C:8]2[C:16]([N:44]2[CH2:49][CH2:48][CH:47]([CH2:50][OH:51])[CH2:46][CH2:45]2)=[O:17])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 4207714-PiperidinemethanolHCID 186270691-(4-fluorobenzyl)-1H-indole-2-carboxylic acid

Product 1

HCID 68380165(1-(4-fluorobenzyl)-1H-indol-2-yl)(4-(hydroxymethyl)piperidin-1-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The following was added sequentially to DMF (10 mL): 1-(4-fluorobenzyl)-1H-indole-2-carboxylic acid (1.175 g, 4.36 mmol), DIPEA (2.29 mL, 13.09 mmol), EDC (1.00 g, 5.24 mmol), and HOBT (802 mg, 5.24 mmol). This solution was allowed to stir at rt for 1.5 h, at which time 4-piperidinemethanol (754 mg, 6.55 mmol) was added. Stirring continued for 22 h at rt, at which time the solution was partitioned between water and 1:1 solution of ethyl acetate:diethyl ether. The organic extract was then washed with saturated aq. sodium carbonate, dried with magnesium sulfate, and concentrated in vacuo. Purification was accomplished via silica gel flash chromatography (100 g silica, 80% EtOAc/Hexanes.) Resulting residue was crystallized via diethyl ether/hexane trituration to give the title compound as a white solid. (Yield: 1.507 g, 4.11 mmol, 94%) 1H NMR (400 MHz, CDCl3) 7.63, 7.37, 7.28-7.22, 7.14, 7.08, 6.91, 6.60, 5.46, 4.65, 4.13, 3.42, 2.76, 1.76-1.54, 1.05, 0.71

Workup

  1. additionwas added
  2. customthe solution was partitioned between water and 1:1 solution of ethyl acetate
  3. extractionThe organic extract
  4. washwas then washed with saturated aq. sodium carbonate
  5. dry with materialdried with magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification
  8. customResulting residue
  9. customwas crystallized via diethyl ether/hexane trituration

Sources & evidence

ORD record
ord-988840caadea41feb7621ebd8dee6997
Source dataset
uspto-grants-2014_09
Patent number
US08846684B2

Reaction notes

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